RESEARCH PROJECT Chronic musculoskeletal pain is extremely common, and pain is the most common symptom in nearly all rheumatic disorders. However, in all chronic pain conditions there is a tremendous disparity between identifiable damage/inflammation in the periphery ? and pain, and classic psychological factors, such as mood or catastrophizing, explain very little of the variance between pain and objective findings. Many individuals with chronic pain have surgery and have continued pain despite excellent surgical results, just as many patients with autoimmune disorders continue to have pain after inflammation is well controlled with biologics. Our CORT Research Project, ?MiCAPP ? Mechanisms of the CentrAlized Pain Phenotype? will have three cohorts with different forms of chronic musculoskeletal pain, one cohort with an autoimmune disorder and inflammatory pain (rheumatoid arthritis), one condition generally considered to be non-inflammatory pain conditions (osteoarthritis), and another considered to be neuropathic (carpal tunnel syndrome). We will demonstrate that in all of these individuals, higher degrees of pain centralization as measured by the 2011 Fibromyalgia (FM) Survey Criteria, will predict non-responsiveness to peripherally-directed analgesic therapies, and will have a common neurobiological signature identifiable on experimental pain testing and functional neuroimaging. Our overall hypothesis is that the current 2011 FM Survey Criteria can identify a subset of individuals across chronic musculoskeletal pain disorders with centralized pain, where the central nervous system (CNS) plays a prominent role in symptom expression, and thus these individuals will be less responsive to interventions aimed at the periphery. Furthermore, we will demonstrate that this centralized pain phenotype has stereotypical underlying neurobiological features across cohorts of individuals with chronic musculoskeletal pain. The Overall Specific Aims that are specifically addressed in this study are: 1) To demonstrate that the current 2011 FM Criteria predict non-responsiveness to peripherally-directed therapies, including a) surgery meant to relieve pain, b) administration of a biologic agent to an individual with an autoimmune disorder, and c) acute and sub-acute administration of opioids; 2) To demonstrate that in all three cohorts, individuals with the highest FM Survey Criteria scores will have the most pronounced neurobiological findings associated with pain centralization, including abnormal QST findings and aberrant findings on functional, chemical and structural neuroimaging; 3) To use the data from the above aims as well as other ongoing studies to develop and pilot test a more efficient and predictive self-report measure of centralization than the 2011 FM Criteria, which we will refer to as a Centralized Pain Index (CPI); and 4) To explore the clinical and mechanistic features of subsets of centralized pain patients that show improvement in centralization following reduction of peripheral nociceptive input (i.e. the central centralization or bottom-up subset) versus those that do not improve (the top down form).